AUTHOR=Bektaş Ömer , Gülşen Murat , Dursun Onur Burak , Tekin Ahmet , Yüksel Deniz , Demir Ercan , Öztürk Gülten , Saltık Sema , Hergüler Özlem , Özçelik Ayşe Aysima , Tan Hüseyin , Özgör Bilge , Ekici Arzu , Yüksel Merve Feyza , Şahin Süleyman , Duman Özgür , Kömür Mustafa , Baydan Figen , Yıldız Edibe Pembegül , Kara Bülent , Yiş Uluç , Kanmaz Seda , Çarman Kürşat Bora , Arslan Elif Acar , Canpolat Mehmet , Güven Ahmet Sami , Öztuncer Gökçen , Ünalp Aycan , Ardıçlı Didem , Karaduman Aynur Ayşe , Zararsız Gökmen , Deda Gülhis ,  Turkish SMA Study Group , Bektaş Ömer , Gülşen Murat , Burak Dursun Onur , Tekin Ahmet , Yüksel Deniz , Demir Ercan , Öztürk Gülten , Saltık Sema , Hergüler Özlem , Aysima Özçelik Ayşe , Tan Hüseyin , Özgör Bilge , Ekici Arzu , Feyza Yüksel Merve , Şahin Süleyman , Duman Özgür , Kömür Mustafa , Baydan Figen , Pembegül Yıldız Edibe , Kara Bülent , Yiş Uluç , Kanmaz Seda , Bora Çarman Kürşat , Acar Arslan Elif , Canpolat Mehmet , Sami Güven Ahmet , Öztuncer Gökçen , Ünalp Aycan , Ardıçlı Didem , Ayşe Karaduman Aynur , Zararsız Gökmen , Yeniay Süt Nurşah , Ünver Olcay , Damla Dilek Tuğçe , Yıldırım Eif , İncecik Faruk , Karadağ Meral , Fatih Bütün Mehmet , Gönüllü Polat Burçin , Güzin Yiğithan , Akif Kılıç Mehmet , Deniz Adnan , Sarıkaya Uzan Gamze , Yılmaz Keskin Sanem , M. Özdemir Fatih , Yarar Coşkun , Yıldız Nihal , Acer Hamit , Çaksen Hüseyin , Aydın Seren , Karaoğlu Pakize , Neşe Çıtak Ayşe , Kendirli Tanıl , Sonel Tur Birkan , Akyüz Gülcan , Bibinoğlu Amirov Ceren , Gül Mert Gülen , Aslan Mahmut , Haspolat Şenay , Ersoy Özlem , Kipoğlu Osman , Alikılıç Defne , Tekgül Hasan , Kaya Ülkühan , Derda Yücel Şen Arife , Özkan Kart Pınar , Per Hüseyin , Aksoy Ayşe , Yılmaz Ünsal , Teber Serap , Göktaş Özben Akıncı , Türkdoğan Dilşad , Uluğ Fitnat , Bilge Serap , Coşkun Orhan , Öztürk Merve , Atmaca Esra , Cansu Ali , Gümüş Hakan , Karadağ Saygı Evrim , Karaca Ömer , Güngör Serdal , Çobanoğlu Nazan , Sezgin Melek , Yıldırım Miraç , Gökdemir Yasemin , Şengenç Esma , Zindar Yılmaz , Yayıcı Özlem , Köken Serkan , Güngör Mesut , Kırık Serkan , Çobanoğulları Direk Meltem , Deda Gülhis 

TITLE=Nusinersen for children with type I spinal muscular atrophy: 4 years’ clinical experience in Turkish cohort

JOURNAL=Frontiers in Neurology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1541507

DOI=10.3389/fneur.2025.1541507

ISSN=1664-2295

ABSTRACT=BackgroundSMA Type 1 is the most severe form of spinal muscular atrophy with early symptom onset, limited motor development, and poor prognosis. Recent genetic-based therapies, such as nusinersen, have transformed disease outcomes. We aimed to evaluate the long-term effects of nusinersen on motor, bulbar, and respiratory functions in both symptomatic and presymptomatic SMA Type 1 patients over a period of up to 4 years.MethodsThis prospective, non-interventional study included 310 patients with genetically confirmed spinal muscular atrophy at 24 pediatric neurology centers in Turkey. Patients treated with nusinersen were divided into five age-based cohorts at treatment initiation: Cohort A (0–3 months), Cohort B (4–6 months), Cohort C (7–12 months), Cohort D (13–24 months), and Cohort E (>24 months). Efficacy was assessed using the CHOP-INTEND and WHO Motor Milestone Scale. This study also analyzed the respiratory support needs, gastrostomy requirements, and mortality rates across cohorts.ResultsPatients treated before 12 months of age showed the most significant improvements in motor milestones, with 58.7% of Cohort A achieving independent sitting. CHOP-INTEND scores increased notably in all cohorts, with the largest improvement observed in Cohort A (93.5%). Ventilator and gastrostomy requirements decreased in the early treated cohorts. Adverse events were rare, with one discontinuation due to hydrocephalus. The overall mortality rate was 21.3%, with most of the deaths occurring within the first year.InterpretationNusinersen treatment initiated before 12 months of age, especially before 3 months of age, yielded the most favorable motor outcomes in patients with SMA type 1. Early initiation is associated with improved motor milestones and reduced need for ventilatory support. However, no significant improvements were observed in the bulbar function or in patients requiring extensive respiratory support.